il-6通过mapk-erk信号通路调节bmscs的软骨定向分化

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1、中国生物化学与分子生物学报http:ISSN1007-76262015年2月CN11-3870/Q153～16031(2):ChineseJournalofBiochemistryandMolecularBiologyDOI:10.13865/j．cnki．cjbmb．2015.02.07IL-6通过MAPK/EＲK信号通路调节BMSCs软骨定向分化杨海杰＊＊，王勉，王磊，程彬峰，冯培，冯志伟＊＊，李志超*(新乡医学院生命科学技术学院，河南省干细胞与生物治疗技术研究中心，河南新乡453003)摘要白细胞介素-6(IL-6)是参与骨

2、髓间充质干细胞(BMSCs)软骨定向分化的重要调节因子．MAPK/EＲK信号通路可介导骨关节炎软骨损伤．然而，IL-6调节BMSCs定向分化为软骨细胞的分子机制尚不清楚．IL-6通过激活MAPK/EＲK信号途径，抑制BMSCs的成软骨分化．本文发现，BMSCs在体外向软骨细胞分化时，Il-6基因表达水平显著下调，同时分泌到培养基中的IL-6蛋白水平亦明显降低．重组IL-6可抑制BMSCs向软骨细胞分化，软骨分化标志蛋白Ｒunx2和Sox9的诱导表达亦相应下调．IL-6可诱导MAPK/EＲK信号通路活化，加入EＲK特异性阻断剂后，Ｒ

3、unx2和Sox9的诱导表达恢复正常．结果提示，IL-6通过激活MAPK/EＲK信号通路抑制BMSCs的软骨细胞分化．炎症因子IL-6对软骨细胞的再生具有不利的影响，该研究为软骨组织工程研究和骨关节炎等软骨疾病的治疗提供有价值的参考．关键词IL-6;间充质干细胞;软骨细胞分化;MAPK信号通路中图分类号Q813IL-6ＲegulatesChondrocyteDifferentiationofBoneMarrow-derivedMesenchymalStemCellsInVitroviaMAPK/EＲKPathwayYANGHai-

4、JieLIZhi-Chao＊＊，＊＊，WANGMian，WANGLei，CHENGBin-Feng，FENGPei，FENGZhi-Wei*(XinxiangMedicalUniversity，Xinxiang453003，Henan，China)CollegeofLifeScienceandTechnology，AbstractInterleukin-6(IL-6)isaregulatorofchondrocytedifferentiation．Themolecularmechanismofbonemarrow-derivedm

5、esenchymalstemcells(BMSCs)differentiationintochondrocyteremainedunclear．TheMAPK/EＲKpathwaymediatesosteoarthritis-elicitedcartilageinjuries．Thisstudyshowed thatMAPK/EＲKinvolvedinIL-6inhibitiononchondrocytedifferentiationofBMSCs．Il-6mＲNAwas significantlydown-regulated，a

6、ndthelevelsofsecretedIL-6proteininmediumwereremarkablydecreased．ＲecombinantIL-6inhibitedchondrogenicdifferentiationofBMSCs， chondrocytemarkersofＲunx2andSox9，togetherwithdecreasedandtheactivationofMAPK/EＲK．EＲK-specificinhibitorrescuedＲunx2andSox9expressionlevelsinBMSCs

7、．TheresultsindicatedthatIL-6inhibitschondrocytedifferentiationofBMSCsviatheactivationofMAPK/EＲKpathway．Ourdatasuggestedthatinflammatoryfactorsmightneedbeconcernedforcartilagetissueengineeringandthetherapyofcartilagediseases，suchasosteoarthritis．Keywordsinterleukin-6;m

8、esenchymalstemcells;chondrocytedifferentiation;MAPKsignalingpathway收稿日期:2014-10-13;接受日期:2014-12-02新乡医学院校内培育基金(No．2013ZD115)资